Nobiletin is a polymethoxylated flavone derived from the peel of citrus fruits. Nobiletin displays anti-inflammatory, anticancer, antioxidative, neuroprotective, cognition enhancing, antidepressant, and anti-obesity properties. In vitro, Nobiletin decreases iNOS expression and levels of NO and also inhibits NF-κB activity. In a variety of cancer cell lines, Nobiletin induces cell cycle arrest and inhibits cellular proliferation through several mechanisms, including inhibition of Ras and MAPK/ERK signaling, downregulation of Bcl-2 and COX-2 levels, upregulation of Bax and caspase-3 expression, and downregulation of matrix metalloproteinase 2 and CXCR4 expression. In aged mice and animal models of Alzheimer’s disease, nobiletin increased glutathione peroxidase and superoxide dismutase activity and decreased phosphorylation of tau, attenuating learning and memory impairments. In other animal models, this compound displays potential use as an antidepressant, attenuating stress-induced deficits in BDNF, TrkB, and synapsin I in the hippocampus. Additionally, nobiletin displays anti-obesity effects in vivo, increasing levels of PPARα/γ, GLUT4, adiponectin, fatty acid synthase, and other enzymes, resulting in decreased body weight gain in overweight animals. Nobiletin may act as a positive allosteric modulator at AMPA receptors by increasing phosphorylation of the GluR1 subunit.